(1R,2S)/(1S,2R)-1-amino-1-ethoxycarbonyl-2-vinylcyclopropane is an intermediate useful for the synthesis of various types of HCV NS3 protease inhibitors and the like, which are currently under development as therapeutic agents for hepatitis C. It is considered that 1,1-di-ethoxycarbonyl-2-vinylcyclopropane and a chiral form of 1-ethoxycarbonyl-2-vinylcyclopropane carboxylic acid are useful as intermediates for synthesizing the (1R,2S)/(1S,2R)-1-amino-1-ethoxycarbonyl-2-vinylcyclopropane.
Patent Document 1 and Example 21 of Patent Document 2 describe that trans-1,4-dibromo-2-butene is allowed to react with diethyl malonate in dichloromethane in the presence of potassium hydroxide (90% flake form) and tricaprylylmethylammonium chloride, so as to obtain 1,1-di-ethoxycarbonyl-2-vinylcyclopropane at a yield of 89%.
In addition, Non Patent Documents 1 to 3 and the like describe a reaction of forming a cyclopropane ring using 1,4-dichloro-2-butene or 1,4-dibromo-2-butene. However, these methods are industrially disadvantageous in terms of yield, and in that dichloromethane that is a halogen compound is used as a solvent and also in that the reaction is a solid-liquid two phase reaction.